Allelic HLA typing refers to sequencing-based typing to determine variations in coding DNA sequences that alter the protein sequences. This is also commonly referred to as high resolution typing or four-digit typing. There are also alleles that bear synonymous mutations and mutations within noncoding DNA, but resolution of these alleles is rarely necessary in clinical practice. In the IMGT/HLA database (1), the majority of HLA alleles are represented by full-length or partial complementary DNA (cDNA) sequences. Some HLA alleles have both cDNA and genomic DNA (gDNA) sequences deposited in the database. For simplicity, we also term a cDNA and/or gDNA sequence of an HLA gene an allele.
HLA typing at the allelic level is typically performed by Sanger sequencing of selected exons of Class I genes (HLA-A, -B and -C) and Class II genes (HLA-DRB1 and -DQB1). HLA typing using exome sequencing (exome-seq) data is in its infancy. Currently, there is no methodology available to perform HLA typing at the allelic level with the necessary accuracy given the typical read length of Illumina and the level of polymorphism within the region. Indeed, a recent report(2) demonstrated that allelic HLA typing is challenging to obtain from Illumina exome-seq data even at high coverage.
The nomenclature of HLA alleles follows the guidelines from the WHO Nomenclature Committee for Factors of the HLA System (http://hla.alleles.org/nomenclature/naming.html).